The lysosomal storage diseases are a group of disorders that manifest from birth to adulthood and result in damage to both somatic organs and the central nervous system. Currently, there are enzyme replacement therapies that have been shown effective in treating Gaucher disease (acid β-glucocerebrosidase (ABG) deficiency), Fabry disease (acid α-galactosidase (GLA) deficiency), and Pompe disease (lysosomal acid α-glucosidase (GAA) deficiency). It is expected that similar therapy will be developed for Niemann-Pick A/B disease type A and B (acid sphingomyelinase (ASM) deficiency). In addition, it has been suggested that presymptomatic initiation of bone marrow transplantation may prevent the neural degeneration observed in Krabbe disease (galactocerebroside β-galactosidase (GALC) deficiency).
For each of these diseases, early therapeutic intervention and thus, early, presymptomatic detection of the disease will be important to maximize treatment benefit. In particular, newborn screening for the enzyme deficiencies associated with the lysosomal storage diseases will provide a greater probability of effective treatment compared to diagnosis of the disease once symptoms have manifested.
A recent paper by Li et al. (Clinical Chemistry (2004) 50: 1785-1796) teaches assays for determining ABG, GLA, GAA, ASM, and GALC enzyme activity from dried blood spots obtained from newborn infants using mass spectrometry. The instant invention is based, in part, on the independent optimization of assays for detection of these enzymes to provide more robust, more reliable methods for determining enzyme activity and disease diagnosis and screening.